This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Currently, high-throughput mass spectrometry requires the existence of curated protein-databases and thereby excludes a growing number of model organisms for which the genome has been sequenced, but not yet annotated. A new experimental approach is therefore developed that aims at covering new proteomes fast, and comprehensively, and independently of how well the particular genome is annotated. To prove the validity of this concept, we apply whole proteome mass spectrometry to an emerging model organism, the starlet sea anemone Nematostella vectensis. The newly developed bioinformatics strategy will represent a computational and biological framework for the analysis of truly complex protein mixtures from organisms with a not yet or incompletely annotated genome.